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Building familial risk into prostate cancer testing decisions

Posted Mar 13 2011 12:00am


The PCPT prostate cancer risk calculator  is a widely used tool designed to help men and their doctors assess whether they should have a prostate biopsy based on the patient’s age, PSA level, and supplementary data. The calculator asks about family history of prostate cancer in one simple question requiring only a Yes/No answer.

However, we are beginning to know a lot more about exactly how family history of prostate cancer really affects risk for other members of a specific family, and this topic has been reviewed in a recent article by Madersbacher et al.  The article raises the question of whether we need to make greater effort to build familial risk factors into calculators like the PCPT prostate cancer risk calculator with a greater degree of sophistication.

Overall, a family history of prostate cancer increases risk for prostate cancer by about 2.5 to 4.0 times for a specific, previously untested individual. However, Madersbacher et al. make a number of more specific points in their article:

  • Between 5 and 10 percent of all prostate cancers appear to be associated with dominantly inherited genetic susceptibility.
  • Identifiable inherited genes contribute about 42 percent to the total risk of developing prostate cancer
  • Specific single nucleotide polymorphisms (SNPs) in combination with family history have been associated with up to a 9-fold increase in risk for prostate cancer.
  • The lifetime risk for developing prostate cancer increases from 12 percent for a man with a father affected at > 60 years of age to between 35 and 45 percent for a man with three or more affected male relatives.
  • The lifetime risk for developing prostate cancer for a man with no family history is only 8 percent.
  • One study has shown that there is a relative risk of developing prostate cancer of 1.93 for men with a history of prostate cancer in any relative, and this risk increases as the degree of relatedness increases.
  • Other studies suggest that the relative risk of developing prostate cancer increases from 1.78 to 1.84 with only a father or brother afflicted to 2.34 if both the brother and the father had prostate cancer. The risk was higher if the relative was diagnosed younger than age 60.
  • In the worst case scenario currently identified, Brandt et al. showed that men aged < 65 years who had three brothers affected by prostate cancer had a hazard ratio (HR) of 23 for a personal diagnosis of prostate cancer.
  • It also appears to be the case that an affected brother confers a higher degree of risk than an affected father.

We probably don’t yet have sufficiently good epidemiological data to be able to construct an accurate calculator that take these levels of risk from family history into account with a high degree of accuracy in building new risk calculators, but we are clearly getting closer to such a possibility.

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